Catheters are tubes or tubing of various diameters that can be inserted into the respective body cavity to be treated. So-called balloon catheters, which are used mainly in angioplasty to dilate or reopen a vessel, have a guide wire that is first inserted into the vessel to be treated. Then a tube which has an undilated folded balloon in a predefined area of the tube, is advanced along the guide wire up to the site of the blood vessel to be treated so that the balloon is placed in the area of the site of the blood vessel to be treated, e.g., where there is a stenosis. Then the balloon is dilated, i.e., unfolded and expanded, so that the site to be treated is reopened or dilated and the flow of body fluid through the blood vessel is no longer hindered or is not hindered to the previous extent. Finally, the balloon is deflated and removed from the blood vessel along the guide wire. At the same time or thereafter, the guide wire is also retracted out of the blood vessel.
For insertion of balloon catheters, the balloon must first be introduced in a folded, i.e., undilated state, into the body cavity to be treated. With the balloon catheters currently in use, the balloons are folded after being shaped and then are secured by applying compressive forces (referred to as impressing) to the folded balloon. The steps required to do so as well as the corresponding device are complex because high temperatures and long impressing times are required in the impressing step. Furthermore, the heat treatment often results in shrinkage of a balloon, thereby altering the dimensions of the balloon. Another disadvantage of this procedure is that the wing shape is lost after the initial dilatation i.e., the balloon is refolded in a defective manner to some extent or is folded inconsistent with its pre-inflation configuration. This is due to the fact that a fold produced in the traditional way stores very little energy on inflation of the balloon so that the refolding tendency in deflation is low. On retraction of a defectively refolded balloon, an increased pull-back force is required. Likewise, an increased force is required to redilate a stent, to reach a side branch through a stent segment or to pass through a second stenosis.
With traditional catheters, the balloon has wings which run parallel to the axis of the balloon. These balloons create an anisotropic bending moment of the folded balloon. The disadvantage of such folding is that the catheter in the area of the balloon is more susceptible to kinking of the catheter and the wings stand up in tight curves on insertion into the body cavity to be treated so that insertion is prevented. After deflation, wings running parallel to the axis of the catheter may also cause unwanted transverse folding when the inside shaft expands with the balloon in a non-plastic manner. This also requires an increased pull-back force.
Furthermore, balloons that are integrally furnished with an active pharmaceutical substance may release residues of the substance to the surrounding body fluid at the wrong point in time, e.g., during retraction in the event of uncontrolled refolding. This may cause adverse effects.
For purposes of the present disclosure, the term “active pharmaceutical substance” (also known as “active therapeutic substance”) means an active ingredient (medication) of plant, animal or synthetic origin or a hormone which is used in a suitable dosage as a therapeutic agent to influence conditions or functions of the body, as a substitute for active ingredients, such as insulin, that are synthesized naturally by the human or animal body and to eliminate disease pathogens, tumors, cancer cells or exogenous substances or to render them harmless. The release of the substance in the environment of the endoprosthesis has a positive effect on the course of healing or counteracts pathological changes in the tissue due to the surgical procedure and/or serves to render malignant cells harmless in oncology.
Such active pharmaceutical substances have an anti-inflammatory and/or antiproliferative and/or spasmolytic effect, so that, for example, restenoses, inflammations or (vascular) spasms can be prevented. In certain exemplary embodiments, such substances may consist of one or more substances from the group of active ingredients consisting of calcium channel blockers, lipid regulators (such as fibrates), immunosuppressants, calcineurin inhibitors (such as tacrolimus), the antiphlogistics (such as cortisone or diclofenac), anti-inflammatories (such as imidazoles), antiallergics, oligonucleotides (such as dODN), estrogens (such as genistein), endothelializing agents (such as fibrin), steroids, proteins, hormones, insulins, cytostatics, peptides, vasodilators (such as sartans) and substances with an antiproliferative action, such as taxols or taxans, in this case, preferably paclitaxel or sirolimus.
German Patent No. 691 19 753 describes a balloon catheter having a catheter body and a balloon arranged along the length of the catheter body. The balloon is also provided with a device for its inflation and deflation from the outside and a device for supplying a medication or a combination of medications for treatment or diagnosis within a hollow organ of a body when the catheter is positioned in the hollow organ and inflated. The supply device has microcapsules on the outside of the balloon where the microcapsules are secured in folds on the balloon such as those formed when the balloon is shrunk. The microcapsules here are designed so that the microcapsules can be ruptured or degraded. The microcapsules open when they remain on the walls of the hollow organ. The capsules may also rupture due to the application of ultrasonic waves.
The disadvantage of the catheter described in German Patent No. 691 19 753 is that microencapsulated medications must be used to implement the dispensing of medications, but microencapsulated medications are expensive and complicated to produce. Furthermore, microencapsulation is not possible for all medications that may be considered. Additionally, a balloon of such a catheter provided with microcapsules has a comparatively large diameter whose profile cannot be used in practice and which makes the catheter rigid and inflexible. Furthermore, the medication can be rubbed off not only at the site to be treated but also on insertion or dilatation of the balloon. This increases the side effects associated with the treatment.
Balloon catheters may also be used to introduce intraluminal endoprostheses to a site to be treated in a body cavity.
Intraluminal endoprostheses in the form of stents are currently widely used because they allow a simple and inexpensive treatment. These stents often have a tubular or hollow cylindrical basic mesh which is open on both longitudinal ends. The basic mesh of such an endoprosthesis is inserted by means of a catheter into the hollow cavity to be treated and is then dilated or released. After removal of the catheter, the endoprosthesis serves to support the body cavity. Such stents have become established, in particular, for treatment of vascular diseases. Through the use of stents, constricted areas in the vessels can be dilated so that the vascular lumen is enlarged.
Intraluminal endoprostheses are often provided with active pharmaceutical substances which are released in the body over a certain period of time.
These active pharmaceutical substances may serve, for example, to prevent restenoses or agglomerations. Due to the release of active pharmaceutical substances with which such intraluminal endoprostheses are provided, it is possible to perform merely a local treatment, i.e., elution of an active ingredient essentially only in the tissue surrounding the intraluminal endoprosthesis. This process is also known as local drug delivery (“LDD”). The treatment site where the active ingredient should manifest its pharmacological effect is thus directly adjacent to the site of implantation of the intraluminal endoprosthesis.
Intraluminal endoprostheses that consist of a material which is subject to biodegradation are currently also in use. For purposes of the present disclosure, biodegradation means hydrolytic, enzymatic or other metabolic degradation processes in a living organism caused mainly by the body fluids coming in contact with the endoprosthesis and leading to a gradual dissolution of at least large portions of the endoprosthesis. The term “biocorrosion” is often synonymous with the term biodegradation. For purposes of the present disclosure, the term “bioabsorption” includes the subsequent absorption of the degradation products by the living organism. Such biodegradable materials may consist of polymers or metals. The abbreviation AMS (absorbable metal stent) is also often used in conjunction with stents. Such stents contain a biodegradable metal, preferably magnesium and/or a magnesium alloy. Other degradable metals that may be used include iron, zinc, tungsten and alloys thereof.
In intraluminal endoprostheses consisting of a biodegradable material and provided with an active pharmaceutical substance, the problem often arises that the active pharmaceutical substances do not adhere properly to the basic mesh of the endoprosthesis or do not function in the desired manner because, in the biodegradation of the endoprosthesis, the pH of the environment may change and/or the endoprosthesis may undergo uncontrolled corrosion and thereby undergo a high degree of penetration. Release of the active pharmaceutical substance thus does not take place in the desired manner or within the desired time frame.